Idiopathic pulmonary fibrosis lung transplant recipients are at increased risk for EBV-associated posttransplant lymphoproliferative disorder and worse survival

Carlo J. Iasella, Spencer A. Winters, Abigail Kois, Jaehee Cho, Stefanie J. Hannan, Ritchie Koshy, Cody A. Moore, Christopher R. Ensor, Elizabeth A. Lendermon, Matthew R. Morrell, Joseph M. Pilewski, Pablo G. Sanchez, Daniel J. Kass, Jonathan K. Alder, S. Mehdi Nouraie, John F. McDyer

Research output: Contribution to journalArticle

Abstract

Epstein-Barr virus (EBV)–associated posttransplant lymphoproliferative disorder (EBV-PTLD) is a serious complication in lung transplant recipients (LTRs) associated with significant mortality. We performed a single-center retrospective study to evaluate the risks for PTLD in LTRs over a 7-year period. Of 611 evaluable LTRs, we identified 28 cases of PTLD, with an incidence of 4.6%. Kaplan-Meier analysis showed a decreased freedom from PTLD in idiopathic pulmonary fibrosis (IPF)-LTRs (P <.02). Using a multivariable Cox proportional hazards model, we found IPF (hazard ratio [HR] 3.51, 95% confidence interval [CI] 1.33-8.21, P =.01) and alemtuzumab induction therapy (HR 2.73, 95% CI 1.10-6.74, P =.03) as risk factors for PTLD, compared to EBV mismatch (HR: 34.43, 95% CI 15.57-76.09, P <.0001). Early PTLD (first year) was associated with alemtuzumab use (P =.04), whereas IPF was a predictor for late PTLD (after first year) (P =.002), after controlling for age and sex. Kaplan-Meier analysis revealed a shorter time to death from PTLD in IPF LTRs compared to other patients (P =.04). The use of alemtuzumab in EBV mismatch was found to particularly increase PTLD risk. Together, our findings identify IPF LTRs as a susceptible population for PTLD. Further studies are required to understand the mechanisms driving PTLD in IPF LTRs and develop strategies to mitigate risk.

Original languageEnglish (US)
Pages (from-to)1439-1446
Number of pages8
JournalAmerican Journal of Transplantation
Volume20
Issue number5
DOIs
StatePublished - May 1 2020

Keywords

  • clinical research/practice
  • hematology/oncology
  • immunosuppression/immune modulation
  • immunosuppressive regimens – induction
  • infection and infectious agents – viral: Epstein-Barr virus (EBV)
  • lung disease
  • lung transplantation/pulmonology
  • posttransplant lymphoproliferative disorder (PTLD)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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  • Cite this

    Iasella, C. J., Winters, S. A., Kois, A., Cho, J., Hannan, S. J., Koshy, R., Moore, C. A., Ensor, C. R., Lendermon, E. A., Morrell, M. R., Pilewski, J. M., Sanchez, P. G., Kass, D. J., Alder, J. K., Nouraie, S. M., & McDyer, J. F. (2020). Idiopathic pulmonary fibrosis lung transplant recipients are at increased risk for EBV-associated posttransplant lymphoproliferative disorder and worse survival. American Journal of Transplantation, 20(5), 1439-1446. https://doi.org/10.1111/ajt.15756